Impaired hemodynamic response to exercise in patients with peripheral artery disease: evidence of a link to inflammation and oxidative stress

Abstract

An exaggerated mean arterial blood pressure (MAP) response to exercise in patients with peripheral artery disease (PAD), likely driven by inflammation and oxidative stress and, perhaps, required to achieve an adequate blood flow response, is well described. However, the blood flow response to exercise in patients with PAD actually remains equivocal. Therefore, eight patients with PAD and eight healthy controls completed 3 min of plantar flexion exercise at both an absolute work rate (WR) (2.7 W, to evaluate blood flow) and a relative intensity (40%WR_max, to evaluate MAP). The exercise-induced change in popliteal artery blood flow (BF, Ultrasound Doppler), MAP (Finapress), and vascular conductance (VC) were quantified. In addition, resting markers of inflammation and oxidative stress were measured in plasma and muscle biopsies. Exercise-induced ΔBF, assessed at 2.7 W, was lower in PAD compared with controls (PAD: 251 ± 150 vs. Controls: 545 ± 187 mL/min, P < 0.001), whereas ΔMAP, assessed at 40%WR_max, was greater for PAD (PAD: 23 ± 14 vs. Controls: 11 ± 6 mmHg, P = 0.028). The exercise-induced ΔVC was lower for PAD during both the absolute WR (PAD: 1.9 ± 1.6 vs. Controls: 4.7 ± 1.9 mL/min/mmHg) and relative intensity exercise (PAD: 1.9 ± 1.8 vs. Controls: 5.0 ± 2.2 mL/min/mmHg) trials (both, P < 0.01). Inflammatory and oxidative stress markers, including plasma interleukin-6 and muscle protein carbonyls, were elevated in PAD (both, P < 0.05), and significantly correlated with the hemodynamic changes during exercise (r = -0.57 to -0.78, P < 0.05). Thus, despite an exaggerated ΔMAP response, patients with PAD exhibit an impaired exercise-induced ΔBF and ΔVC, and both inflammation and oxidative stress likely play a role in this attenuated hemodynamic response.

Keywords: blood flow; exercise pressor response; peripheral vascular disease.

Figure 1.

Hemodynamic responses to absolute work rate dynamic plantarflexion exercise. Individual and group changes in popliteal artery blood flow (A), mean arterial pressure (B), and vascular conductance (C) in patients with peripheral artery disease (PAD, open symbols), and healthy controls (closed symbols) during exercise at an absolute work rate of 2.7 W. Dashed line in the box plots represents the mean and the solid line represents the median. Upper and lower limits of the box plot represent the 75th and 25th percentile, respectively. *Significantly different from PAD (P < 0.05). Of note, in B, the significant difference between patients with PAD and controls was maintained with the uppermost patient data point removed (P < 0.01).

Figure 2.

Hemodynamic responses to relative intensity dynamic plantarflexion exercise. Individual and group changes in popliteal artery blood flow (A), mean arterial pressure (B), and vascular conductance (C) in patients with peripheral artery disease (PAD, open symbols) and healthy controls (closed symbols) during exercise at relative intensity of 40% peak power. The dashed line in box plots represents the mean and the solid line represents the median. Upper and lower limits of the box plot represent the 75th and 25th percentile, respectively. *Significantly different from PAD (P < 0.05). Of note, in B, the significant difference between patients with PAD and controls was maintained with the uppermost patient data point removed (P = 0.034).

Figure 3.

Relationships between the exercise-induced change in vascular conductance and markers of inflammation and oxidative stress. Vascular conductance was related to plasma interleukin-6 (a systemic marker of inflammation; A and C) and intramuscular protein carbonyl (indicative of intramuscular oxidative stress; B and D) during both the absolute work rate trial (2.7 W; left) and the relative intensity exercise trial (40% peak power; right). Individual data represent both patients with peripheral artery disease (open circles) and healthy controls (filled circles). The solid lines represent the overall correlations (coefficients and P values inset).